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1.
Int J Nanomedicine ; 15: 6327-6338, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922004

RESUMO

Purpose: To construct a three-dimensional (3D) culture model of adenovirus in vitro using the nanoself-assembling peptide RADA16-I as a 3D cell culture scaffold combined with virology experimental technology to provide a novel research method for virus isolation and culture, pathogenesis research, antiviral drug screening and vaccine preparation. Methods: The nanoself-assembling peptide RADA16-I was used as a 3D scaffold material for 293T cell culture, and adenovirus was cultured in the cells. The growth, morphological characteristics and pathological effects of 3D-cultured 293T cells after adenovirus infection were observed with an inverted microscope and MTS. The proliferation of adenovirus in 293T cells was observed by TEM and detected by qPCR. The levels of TNF-α and IL-8 secreted by adenovirus-infected 293T cells in the RADA16-I 3D culture system were detected by ELISA. Results: The 293T cells grew well in the RADA16-I 3D culture system for a prolonged period of time. The adenovirus infection persisted for a long time with multiple proliferation peaks, which closely resembled those of in vivo infections. The adenovirus virions amplified in the 3D system remained infectious. There were multiple secretion peaks of TNF-α and IL-8 secretion levels in adenovirus-infected 293T cells cultured in 3D culture systems. Conclusion: The nanoself-assembling peptide RADA16-I can be used as a 3D scaffold for adenovirus isolation, culture and research. The 3D culture system shows more realistic in vivo effects than two-dimensional (2D) culture.


Assuntos
Infecções por Adenoviridae/virologia , Adenoviridae/fisiologia , Técnicas de Cultura de Células/métodos , Nanopartículas/química , Peptídeos/química , Adenoviridae/crescimento & desenvolvimento , Adenoviridae/ultraestrutura , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Células HEK293 , Humanos , Vírion/ultraestrutura
2.
PLoS One ; 15(9): e0234532, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32991587

RESUMO

This article describes the isolation, molecular characterization, and genotyping of two fowl adenovirus (FAdVs) strains with GenBank Accession numbers (MT478054, JSN-G033-18-L and MT478055, JSN-G033-18-B) obtained from the internal organs of black grouse (Lyrurus tetrix). This study also reveals the first confirmation of fowl adenovirus in Poland, supporting one of the hypotheses about the probability of fowl adenovirus interspecies transmission. The adenovirus strain sequences were investigated via phylogenetic analysis and were found to have an overall mean pairwise distance of 2.189. The heterogeneity, Relative Synonymous Codon Usage (RSCU), codon composition, and nucleotide frequencies were examined. Statistical analyses and Tajima's test for the examined sequences were carried out. The Maximum Likelihood for the examined sequences substitutions was performed. The results of the sequence analysis identified MT478054, JSN-G033-18-L and MT478055, JSN-G033-18-B as strains of fowl adenovirus 2/11/D, with the Fowl adenovirus D complete sequence showing a 93% match. Wild birds may act as a natural reservoir for FAdVs and likely play an important role in the spreading of these viruses in the environment. The findings reported here suggest horizontal transmission within and between avian species.


Assuntos
Infecções por Adenoviridae/veterinária , Aviadenovirus/isolamento & purificação , Galliformes/virologia , Doenças das Aves Domésticas/virologia , Infecções por Adenoviridae/virologia , Animais , Aviadenovirus/classificação , Aviadenovirus/genética , Uso do Códon , DNA Viral/genética , Filogenia , Polônia
3.
BMC Infect Dis ; 20(1): 633, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847534

RESUMO

BACKGROUND: Cases of refractory Mycoplasma pneumoniae pneumonia have been increasing recently; however, whether viral coinfection or macrolide-resistant M. infection contribute to the development of refractory M. pneumoniae pneumonia remains unclear. This study aimed to investigate the impacts of viral coinfection and macrolide-resistant M. pneumoniae infection on M. pneumoniae pneumonia in hospitalized children and build a model to predict a severe disease course. METHODS: Nasopharyngeal swabs or sputum specimens were collected from patients with community-acquired pneumonia meeting our protocol who were admitted to Shanghai Children's Medical Center from December 1, 2016, to May 31, 2019. The specimens were tested with the FilmArray Respiratory Panel, a multiplex polymerase chain reaction assay that detects 16 viruses, Bordetella pertussis, M. pneumoniae, and Chlamydophila pneumoniae. Univariate and multivariate logistic regression models were used to identify the risk factors for adenovirus coinfection and macrolide-resistant mycoplasma infection. RESULTS: Among the 107 M. pneumoniae pneumonia patients, the coinfection rate was 56.07%, and 60 (60/107, 56.07%) patients were infected by drug-resistant M. pneumoniae. Adenovirus was the most prevalent coinfecting organism, accounting for 22.43% (24/107). The classification tree confirmed that viral coinfection was more common in patients younger than 3 years old. Adenovirus coinfection and drug-resistant M. pneumoniae infection occurred more commonly in patients with refractory M. pneumoniae pneumonia (P = 0.019; P = 0.001). A prediction model including wheezing, lung consolidation and extrapulmonary complications was used to predict adenovirus coinfection. The area under the receiver operating characteristic curve of the prediction model was 0.795 (95% CI 0.679-0.893, P < 0.001). A prolonged fever duration after the application of macrolides for 48 h was found more commonly in patients infected by drug-resistant M. pneumoniae (P = 0.002). A fever duration longer than 7 days was an independent risk factor for drug-resistant Mycoplasma infection (OR = 3.500, 95% CI = 1.310-9.353, P = 0.012). CONCLUSIONS: The occurrence of refractory M. pneumoniae pneumonia is associated with adenovirus coinfection and infection by drug-resistant M. pneumoniae. A prediction model combining wheezing, extrapulmonary complications and lung consolidation can be used to predict adenovirus coinfection in children with M. pneumoniae pneumonia. A prolonged fever duration indicates drug-resistant M. pneumoniae infection, and a reasonable change in antibiotics is necessary.


Assuntos
Infecções por Adenoviridae/epidemiologia , Adenoviridae/genética , Antibacterianos/uso terapêutico , Coinfecção/epidemiologia , Farmacorresistência Bacteriana , Macrolídeos/uso terapêutico , Mycoplasma pneumoniae/genética , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/epidemiologia , Infecções por Adenoviridae/virologia , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Coinfecção/virologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Feminino , Hospitalização , Humanos , Lactente , Masculino , Reação em Cadeia da Polimerase Multiplex , Mycoplasma pneumoniae/efeitos dos fármacos , Pneumonia por Mycoplasma/virologia , Prevalência , Prognóstico , Resultado do Tratamento
4.
J Virol ; 94(17)2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32611755

RESUMO

Recently, the disease of hepatitis-hydropericardium syndrome (HPS) caused by serotype 4 fowl adenovirus (FAdV-4) has spread widely and resulted in huge economic losses to the poultry industry. Although the genome of FAdV-4 has two fiber genes (fiber-1 and fiber-2), the exact role of the genes in the infection of FAdV-4 is barely known. In this study, through superinfection resistance analysis and an interfering assay, we found that fiber-1, but not fiber-2, was the key factor for directly triggering the infection of FAdV-4. The truncation analysis further revealed that both of the shaft and knob domains of fiber-1 were required for the infection. Moreover, the sera against the knob domain were able to block FAdV-4 infection, and the knob-containing fusion protein provided efficient protection against the lethal challenge of FAdV-4 in chickens. All the data demonstrated the significant roles of fiber-1 and its knob domain in directly mediating the infection of FAdV-4, which established a foundation for identifying the receptor of FAdV-4 and developing efficient vaccines against FAdV-4.IMPORTANCE Among 12 serotypes of fowl adenovirus (FAdV), FAdV-1, FAdV-4, and FAdV-10 all carry two fiber genes (i.e., fiber-1 and fiber-2), whereas other serotypes have only one. As important viral surface proteins, the fibers play vital roles in the infection and pathogenesis of FAdV. However, the importance of the fibers to the infection and pathogenesis of FAdV may be different from each other. Recent studies reveal that fiber-2 is identified as a determinant of virulence, but which fiber triggers the infection of FAdV-4 remains unknown. In this study, fiber-1 was identified as a key factor for directly mediating the infection of FAdV-4 through its shaft and knob domains, whereas fiber-2 did not play a role in triggering FAdV-4 infection. The results suggest that fiber-1 and its knob domain may serve as a target for identifying the receptor of FAdV-4 and developing efficient drugs or vaccines against FAdV-4.


Assuntos
Infecções por Adenoviridae/virologia , Adenoviridae/genética , Adenoviridae/metabolismo , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Doenças das Aves Domésticas/virologia , Adenoviridae/patogenicidade , Infecções por Adenoviridae/imunologia , Infecções por Adenoviridae/patologia , Infecções por Adenoviridae/prevenção & controle , Animais , Anticorpos Antivirais , Linhagem Celular , Galinhas/virologia , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/patologia , Doenças das Aves Domésticas/prevenção & controle , Domínios Proteicos , Sorogrupo , Vacinas Virais/imunologia
5.
PLoS One ; 15(7): e0236175, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697798

RESUMO

Adenoviruses cause upper respiratory infections, conjunctivitis, keratitis, and gastrointestinal illness. These can be fatal in immunocompromised individuals. Adenoviruses have also been engineered into viral vectors to deliver therapeutic genes or induce immunity as vaccine carriers. The success of ocular gene therapy is driven partly by the immunologic and biochemical influences of the intraocular environment. We have shown that versican and hyaluronan modulate adenoviral vector transgene expression through CD44 signaling. Herein we explored the role of these pathways on virus replication and viral protein expression of wild type adenovirus. We report that the addition of vitreous humor (which contains both versican and hyaluronan) increases viral hexon protein levels. Vitreous humor also increased wild type adenovirus DNA replication in vitro. Metalloproteinase and γ-secretase inhibitors, which inhibit CD44 proteolytic activation, blocked adenoviral replication in vitro. Similarly, protein kinase C and RhoA kinase inhibitors, both proteins associated with CD44 mediated pathways, also inhibited wild type adenoviral replication in vitro. Application of metalloproteinase and γ-secretase inhibitors to human conjunctival explants sharply decreased adenoviral vector gene expression. Our results demonstrate that pharmacologic delivery of these inhibitors is easily achievable. The inhibition of these enzymes should be explored as potential therapies of wild type adenoviral infections.


Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Adenoviridae/efeitos dos fármacos , Antivirais/farmacologia , Vetores Genéticos/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Adenoviridae/fisiologia , Infecções por Adenoviridae/virologia , Administração Oftálmica , Amidas/farmacologia , Amidas/uso terapêutico , Antivirais/uso terapêutico , Túnica Conjuntiva/metabolismo , DNA Viral/genética , DNA Viral/isolamento & purificação , Diaminas/farmacologia , Diaminas/uso terapêutico , Dipeptídeos/farmacologia , Dipeptídeos/uso terapêutico , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Vetores Genéticos/fisiologia , Células HeLa , Humanos , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/metabolismo , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/uso terapêutico , Indóis/farmacologia , Indóis/uso terapêutico , Maleimidas/farmacologia , Maleimidas/uso terapêutico , Metaloproteases/antagonistas & inibidores , Metaloproteases/metabolismo , Permeabilidade , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Proteólise/efeitos dos fármacos , Piridinas/farmacologia , Piridinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Versicanas/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo , Corpo Vítreo/metabolismo , Quinases Associadas a rho/metabolismo
6.
J Vet Diagn Invest ; 32(4): 598-603, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32560597

RESUMO

A 61-d-old fennec fox (Vulpes zerda), 11 d after receiving a multivalent, modified-live virus vaccine containing canine distemper virus (CDV), canine adenovirus 2 (CAdV-2), parainfluenza virus, parvovirus, and canine coronavirus, developed oculonasal discharge, and subsequently convulsions, and hemoptysis, and died. Microscopic changes in the cerebrum were evident, including neuronal degeneration and necrosis; intracytoplasmic eosinophilic inclusion bodies were observed in astrocytes. CDV was detected in the brain tissue by immunohistochemistry. Pulmonary lesions of multifocal necrotizing bronchopneumonia had Cowdry type A intranuclear inclusions in the bronchial epithelial cells. Electron microscopy revealed crystalline arrays of adenovirus-like particles within the intranuclear inclusions. Additionally, the hemagglutinin gene of CDV and the CAdV-2 DNA polymerase gene were detected in the fennec fox; sequence analysis showed 100% identity with those of the vaccine strain viruses. To our knowledge, vaccine-induced CDV and CAdV-2 coinfections using molecular analysis have not been reported previously. Therefore, vaccine strains should be considered prior to CDV vaccination in nondomestic carnivores.


Assuntos
Infecções por Adenoviridae/veterinária , Adenovirus Caninos/isolamento & purificação , Coinfecção/veterinária , Vírus da Cinomose Canina/isolamento & purificação , Raposas/virologia , Infecções por Adenoviridae/virologia , Animais , Encéfalo/virologia , Cinomose/virologia , Vírus da Cinomose Canina/genética , Evolução Fatal , Infecções por Parvoviridae/veterinária , Infecções por Parvoviridae/virologia , Vacinação/veterinária , Vacinas Atenuadas , Vacinas Virais/imunologia
7.
Virology ; 546: 25-37, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32452415

RESUMO

Bovine adenovirus-3 (BAdV-3) is a non enveloped, icosahedral DNA virus containing a genome of 34446 bps. The intermediate region of BAdV-3 encodes pIX and IVa2 proteins. Here, we report the characterization of BAdV-3 IVa2. Anti-IVa2 serum detected a 50 kDa protein at 24-48 h post infection in BAdV-3 infected cells. The IVa2 localizes to nucleus and nucleolus of BAdV-3 infected cells. Analysis of mutant IVa2 demonstrated that amino acids 1-25 and 373-448 are required for nuclear and nucleolar localization of IVa2, respectively. The nuclear import of IVa2 utilize importin α -1 of importin nuclear import pathway. Although deletion/substitution of amino acids 4-18 is sufficient to abrogate the nuclear localization of IVa2, amino acids 1-25 are required for nuclear localization of a cytoplasmic protein. Furthermore, we demonstrate that amino acids 1-25 and 120-140 of IVa2 interact with importin α-1 and pV proteins, respectively in BAdV-3 infected cells.


Assuntos
Infecções por Adenoviridae/veterinária , Doenças dos Bovinos/virologia , Nucléolo Celular/virologia , Mastadenovirus/metabolismo , Proteínas Virais/química , Proteínas Virais/metabolismo , Transporte Ativo do Núcleo Celular , Infecções por Adenoviridae/genética , Infecções por Adenoviridae/metabolismo , Infecções por Adenoviridae/virologia , Motivos de Aminoácidos , Animais , Bovinos , Doenças dos Bovinos/genética , Doenças dos Bovinos/metabolismo , Nucléolo Celular/genética , Nucléolo Celular/metabolismo , Núcleo Celular/genética , Núcleo Celular/metabolismo , Núcleo Celular/virologia , Genoma Viral , Carioferinas/genética , Carioferinas/metabolismo , Mastadenovirus/química , Mastadenovirus/genética , Ligação Proteica , Transporte Proteico , Proteínas Virais/genética
8.
Nat Commun ; 11(1): 1997, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32332742

RESUMO

Persistent viruses cause chronic disease, and threaten the lives of immunosuppressed individuals. Here, we elucidate a mechanism supporting the persistence of human adenovirus (AdV), a virus that can kill immunosuppressed patients. Cell biological analyses, genetics and chemical interference demonstrate that one of five AdV membrane proteins, the E3-19K glycoprotein specifically triggers the unfolded protein response (UPR) sensor IRE1α in the endoplasmic reticulum (ER), but not other UPR sensors, such as protein kinase R-like ER kinase (PERK) and activating transcription factor 6 (ATF6). The E3-19K lumenal domain activates the IRE1α nuclease, which initiates mRNA splicing of X-box binding protein-1 (XBP1). XBP1s binds to the viral E1A-enhancer/promoter sequence, and boosts E1A transcription, E3-19K levels and lytic infection. Inhibition of IRE1α nuclease interrupts the five components feedforward loop, E1A, E3-19K, IRE1α, XBP1s, E1A enhancer/promoter. This loop sustains persistent infection in the presence of the immune activator interferon, and lytic infection in the absence of interferon.


Assuntos
Infecções por Adenoviridae/imunologia , Adenoviridae/patogenicidade , Proteínas E3 de Adenovirus/metabolismo , Endorribonucleases/metabolismo , Regulação Viral da Expressão Gênica/imunologia , Proteínas Serina-Treonina Quinases/metabolismo , Células A549 , Adenoviridae/genética , Adenoviridae/imunologia , Infecções por Adenoviridae/genética , Infecções por Adenoviridae/virologia , Proteínas E1A de Adenovirus/genética , Doença Crônica , Retículo Endoplasmático/metabolismo , Endorribonucleases/genética , Técnicas de Silenciamento de Genes , Técnicas de Inativação de Genes , Células HeLa , Interações Hospedeiro-Patógeno/genética , Humanos , Hospedeiro Imunocomprometido , Interferon gama/genética , Interferon gama/imunologia , Interferon gama/metabolismo , Proteínas Serina-Treonina Quinases/genética , Processamento de RNA , Latência Viral , Liberação de Vírus/genética , Proteína 1 de Ligação a X-Box/genética
9.
Res Vet Sci ; 131: 31-37, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32283442

RESUMO

Hepatitis-hydropericardium syndrome (HHS) caused by hypervirulent fowl adenovirus 4 (FAdV-4) have been causing great economic losses to Chinese poultry industry since 2015. Elucidation of the pathogenesis of FAdV-4 will lay solid foundation for developing attenuated FAdV-4 vaccine and vaccine vector. Our previous study has demonstrated that the increased virulence of hypervirulent FAdV-4 was associated with fiber-2 and hexon genes. However, the roles of fiber-1 and penton in virulence of FAdV-4 have never been elucidated. To further investigate the roles of the major structural proteins fiber-1 and penton in the virulence of hypervirulent FAdV-4, the fiber-1- and penton-replaced mutant viruses were constructed based on the FAdV-4 infectious clones of hypervirulent strain HNJZ using Redαß recombineering techniques. The pathogenicity of the rescued viruses was evaluated in 3-week-old SPF chickens. Chickens infected with the rescued recombinant viruses carrying the fiber-1 or penton base gene from a nonpathogenic strain ON1 developed similar clinical signs to the natural hypervirulent FAdV-4 infection, including HHS-indicative gross lesions and histopathological changes in sick/dead chickens. Our results suggested that the increased virulence of hypervirulent FAdV-4 was independent of fiber-1 and penton. The detailed pathogenesis of FAdV-4 and the roles of fiber-1 and penton in the viral replication and infection process need to be further explored.


Assuntos
Infecções por Adenoviridae/veterinária , Adenoviridae/patogenicidade , Doenças das Aves Domésticas/virologia , Proteínas Virais/metabolismo , Adenoviridae/genética , Infecções por Adenoviridae/virologia , Animais , Galinhas/imunologia , Virulência/genética
10.
Avian Dis ; 64(1): 16-22, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32267121

RESUMO

Hydropericardium syndrome (HPS) is caused by fowl adenovirus serotype 4 (FAdV-4). HPS has caused outbreaks in Chinese populations of broiler chickens since 2015. However, little is known about the molecular mechanisms underlying HPS. In this study, we used transcriptomic analysis to screen differentially expressed genes (DEGs) in the livers of FAdV-4-infected and noninfected chicks. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the gene network associated with the arginine metabolism pathway was enriched in livers infected by FAdV-4; 10 genes were downregulated and 8 genes were upregulated in these livers when compared to noninfected livers. The DEGs identified in livers were reanalyzed by real-time fluorescence quantitative PCR (qPCR); results indicated that the mRNA levels of the DEGs concurred with the data derived from KEGG analysis. Next, we used qPCR to detect the DEGs of the arginine metabolism pathway in a hepatocellular carcinoma cell line (LMH) after infection with FAdV-4 for 24 hr; this also indicated that the mRNA levels of the DEGs concurred with that seen in the liver. We also used si-RNA oligonucleotides to knock down the mRNA levels of iNOS in LMH cells infected with FAdV-4 and found that the viral load of FAdV-4 was increased. Further investigation revealed that the addition of 240 µg/ml of arginine into the culture medium of LMH cells infected with FAdV-4 for 24 hr led to a significant increase in the mRNA levels of iNOS but a significant reduction in the viral load of FAdV-4. Therefore, our data indicated that when broiler chickens become infected with FAdV-4, the arginine metabolic pathway in the liver becomes dysfunctional and the iNOS mRNA level decreases. This will add benefit to the replication of FAdV-4 but can be inhibited by the addition of an appropriate amount of arginine.


Assuntos
Infecções por Adenoviridae/veterinária , Arginina/metabolismo , Galinhas , Adenovirus A das Aves/fisiologia , Doenças das Aves Domésticas/virologia , Replicação Viral , Infecções por Adenoviridae/virologia , Animais , Feminino , Adenovirus A das Aves/classificação , Fígado/virologia , Sorogrupo , Carga Viral
12.
PLoS Negl Trop Dis ; 14(2): e0008027, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32049958

RESUMO

Zika virus (ZIKV) has spread in many countries or territories causing severe neurologic complications with potential fatal outcomes. The small primate common marmosets are susceptible to ZIKV, mimicking key features of human infection. Here, a novel simian adenovirus type 23 vector-based vaccine expressing ZIKV pre-membrane-envelope proteins (Sad23L-prM-E) was produced in high infectious titer. Due to determination of immunogenicity in mice, a single-dose of 3×108 PFU Sad23L-prM-E vaccine was intramuscularly inoculated to marmosets. This vaccine raised antibody titers of 104.07 E-specific and 103.13 neutralizing antibody (NAb), as well as robust specific IFN-γ secreting T-cell response (1,219 SFCs/106 cells) to E peptides. The vaccinated marmosets, upon challenge with a high dose of ZIKV (105 PFU) six weeks post prime immunization, reduced viremia by more than 100 folds, and the low level of detectable viral RNA (<103 copies/ml) in blood, saliva, urine and feces was promptly eliminated when the secondary NAb (titer >103.66) and T-cell response (>726 SFCs/106 PBMCs) were acquired 1-2 weeks post exposure to ZIKV, while non-vaccinated control marmosets developed long-term high titer of ZIKV (105.73 copies/ml) (P<0.05). No significant pathological lesions were observed in marmoset tissues. Sad23L-prM-E vaccine was detectable in spleen, liver and PBMCs at least 4 months post challenge. In conclusion, a prime immunization with Sad23L-prM-E vaccine was able to protect marmosets against ZIKV infection when exposed to a high dose of ZIKV. This Sad23L-prM-E vaccine is a promising vaccine candidate for prevention of ZIKV infection in humans.


Assuntos
Infecções por Adenoviridae/veterinária , Adenovirus dos Símios/classificação , Callithrix , Doenças dos Macacos/virologia , Infecção por Zika virus/veterinária , Infecções por Adenoviridae/imunologia , Infecções por Adenoviridae/virologia , Animais , Doenças dos Macacos/imunologia , Infecção por Zika virus/imunologia
13.
PLoS One ; 15(2): e0229415, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32109945

RESUMO

Avian adenoviruses (AdVs) are a very diverse group of pathogens causing diseases in poultry and wild birds. Wild birds, endangered by habitat loss and habitat fragmentation in the tropical forests, are recognised to play a role in the transmission of various AdVs. In this study, two novel, hitherto unknown AdVs were described from faecal samples of smooth-billed ani and tropical screech owl. The former was classified into genus Aviadenovirus, the latter into genus Atadenovirus, and both viruses most probably represent new AdV species as well. These results show that there is very limited information about the biodiversity of AdVs in tropical wild birds, though viruses might have a major effect on the population of their hosts or endanger even domesticated animals. Surveys like this provide new insights into the diversity, evolution, host variety, and distribution of avian AdVs.


Assuntos
Infecções por Adenoviridae/veterinária , Adenoviridae/genética , Adenoviridae/isolamento & purificação , Aves/virologia , DNA Viral/análise , Estrigiformes/virologia , Adenoviridae/classificação , Infecções por Adenoviridae/virologia , Animais , Aves/genética , DNA Viral/genética , Filogenia , Estrigiformes/genética
14.
J Virol ; 94(10)2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32102889

RESUMO

Human adenoviruses have many attractive features for gene therapy applications. However, the high prevalence of preexisting immunity against these viruses in general populations worldwide has greatly limited their clinical utility. In addition, the most commonly used human adenovirus, human adenovirus subgroup C serotype 5 (HAd5), when systemically administered, triggers systemic inflammation and toxicity, with the liver being the most severely affected organ. Here, we evaluated the utility and safety of a new low-seroprevalence gorilla adenovirus (GAd; GC46) as a gene transfer vector in mice. Biodistribution studies revealed that systemically administered GAd had a selective and robust lung endothelial cell (EC) tropism with minimal vector expression throughout many other organs and tissues. Administration of a high dose of GAd accomplished extensive transgene expression in the lung yet elicited no detectable inflammatory histopathology in this organ. Furthermore, GAd, unlike HAd5, did not exhibit hepatotropism or induce liver inflammatory toxicity in mice, demonstrating the exceptional safety profile of the vector vis-à-vis systemic utility. We further demonstrated that the GAd capsid fiber shared the flexibility of the HAd5 equivalent for permitting genetic modification; GAd with the pan-EC-targeting ligand myeloid cell-binding peptide (MBP) incorporated in the capsid displayed a reduced lung tropism and efficiently retargeted gene expression to vascular beds in other organs.IMPORTANCE In the aggregate, our mouse studies suggest that GAd is a promising gene therapy vector that utilizes lung ECs as a source of therapeutic payload production and a highly desirable toxicity profile. Further genetic engineering of the GAd capsid holds the promise of in vivo vector tropism modification and targeting.


Assuntos
Adenoviridae/genética , Capsídeo/metabolismo , Vetores Genéticos , Gorilla gorilla/virologia , Pulmão/metabolismo , Tropismo/imunologia , Infecções por Adenoviridae/patologia , Infecções por Adenoviridae/virologia , Adenovírus Humanos/genética , Animais , Proteínas do Capsídeo/genética , Células Endoteliais , Expressão Gênica , Terapia Genética , Fígado , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos C57BL , Estudos Soroepidemiológicos , Transdução Genética , Transgenes , Vírion
15.
Medicine (Baltimore) ; 99(2): e18504, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914021

RESUMO

We aimed to evaluate the clinical significance of bacterial coexistence and the coinfection dynamics between bacteria and respiratory viruses among young children. We retrospectively analyzed clinical data from children aged < 5 years hospitalized with a community-acquired single respiratory viral infection of influenza, adenovirus, or RSV during 2 recent consecutive influenza seasons. Remnant respiratory specimens were used for bacterial PCR targeting Moraxella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus.A total of 102 children were included; median age was 0.8 years and 44.1% had underlying comorbidities. Overall, 6.8% (7/102) of cases were classified as severe diseases requiring intensive care unit admission and/or mechanical ventilation and ranged from 8.8% for a patient with RSV and 7.6% for those with adenovirus to 0% for those with influenza viruses. The overall viral-bacterial codetection rate was 59.8% (61/102); M catarrhalis was the most frequent (33.3%), followed by H influenzae (31.4%). Influenza cases showed higher bacterial codetection rates (80.0%; 8/10) compared with those with adenoviruses (69.2%; 9/13) and RSV (55.7%; 44/79). S pneumoniae and H influenzae codetections were associated with reduced severity (aOR, 0.24; 95% CI, 0.07-0.89), and reduced risk of wheezing (aOR, 0.36; 95% CI, 0.13-0.98), respectively.We observed the interactions between respiratory viruses and bacteria and the clinical significance of viral-bacterial coexistence in upper airway on disease severity. Future study will be necessary to elucidate the active interactions between different viruses and bacteria and give clues to risk stratified strategy in the management of respiratory infections among young children.


Assuntos
Adenoviridae/isolamento & purificação , Haemophilus influenzae/isolamento & purificação , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/virologia , Bactérias/genética , Pré-Escolar , Coinfecção/microbiologia , Coinfecção/virologia , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/virologia , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Influenza Humana/diagnóstico , Influenza Humana/virologia , Masculino , Prevalência , Sons Respiratórios/diagnóstico , Sons Respiratórios/etiologia , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/genética , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Staphylococcus aureus/isolamento & purificação , Streptococcus pneumoniae/isolamento & purificação , Vírus/genética
16.
PLoS One ; 15(1): e0226203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31910439

RESUMO

Adenoviruses are double-strained DNA viruses found in a great number of vertebrates, including humans. In order to understand their transmission dynamics, it is crucial, even from a human health perspective, to investigate how host traits influence their prevalence. Bats are important reservoirs for adenoviruses, and here we use the results of recent screenings in Western Europe to evaluate the association between characteristic traits of bat species and their probability of hosting adenoviruses, taking into account their phylogenetic relationships. Across species, we found an important phylogenetic component in the presence of adenoviruses and mating strategy as the most determinant factor conditioning the prevalence of adenoviruses across bat species. Contrary to other more stable mating strategies (e.g. harems), swarming could hinder transmission of adenoviruses since this strategy implies that contacts between individuals are too short. Alternatively, bat species with more promiscuous behavior may develop a stronger immune system. Outstandingly high prevalence of adenoviruses was reported for the Iberian species Pipistrellus pygmaeus, P. kuhlii and Nyctalus lasiopterus and we found that in the latter, males were more likely to be infected by adenoviruses than females, due to the immunosuppressing consequence of testosterone during the mating season. As a general trend across species, we found that the number of adenoviruses positive individuals was different across localities and that the difference in prevalence between populations was correlated with their geographic distances for two of the three studied bat species (P. pygmaeus and P.kuhlii). These results increase our knowledge about the transmission mechanisms of adenoviruses.


Assuntos
Infecções por Adenoviridae/veterinária , Adenoviridae/classificação , Adenoviridae/genética , Quirópteros/fisiologia , Quirópteros/virologia , Preferência de Acasalamento Animal , Comportamento Sexual Animal , Adenoviridae/isolamento & purificação , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/virologia , Animais , Quirópteros/psicologia , Europa (Continente)/epidemiologia , Feminino , Masculino , Filogenia , Prevalência
17.
J Zoo Wildl Med ; 50(4): 769-777, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926506

RESUMO

Eastern box turtles (Terrapene carolina carolina) are a native North American species with a declining population trend that may be attributable to habitat fragmentation, vehicle collisions, and disease. Adenoviral infections can cause significant morbidity and mortality in captive reptile populations. Adenoviruses have been documented in box turtles, but their occurrence and impact in wild populations are unknown. A disease survey was performed at The Wildlife Center of Virginia, USA, to assess the prevalence of box turtle adenovirus (BTAdV) in wild eastern box turtles and evaluate potential associations with clinical disease. Swabs from the oral cavity, including the choanal slit, and the cloaca were collected from 106 eastern box turtles from July 2015 through June 2016. The quantitative polymerase chain reaction (qPCR) primer detected both ornate box turtle adenovirus 1 and eastern box turtle adenovirus. The resulting qPCR adenovirus prevalence was 55.7% (n = 59). Most animals (99.3%) that tested positive for BTAdV had fewer than 100 viral copies/ng DNA. This study did not find a statistically significant association between cause of admission, age, sex, outcome, and BTAdV qPCR status. However, the probability of BTAdV detection was 1.5 times higher in rehabilitation turtles compared with wild turtles (P = 0.01). Albumin was significantly lower in qPCR BTAdV-positive turtles (P = 0.007). Hypoalbuminemia is not generally associated with adenovirus infections in other species, and no obvious clinical cause for this abnormality was identified. The results of this study suggest that eastern box turtles may harbor BTAdV infections at low levels and that infection is rarely associated with clinical disease, potentially identifying BTAdV as a host-adapted pathogen. Future studies should focus on this pathogen's ability to induce clinical disease and its potential impact on recovery efforts for this species.


Assuntos
Infecções por Adenoviridae/veterinária , Adenoviridae/classificação , Adenoviridae/isolamento & purificação , Tartarugas/virologia , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/virologia , Animais , Animais Selvagens , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Masculino , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/veterinária , Prevalência , Sensibilidade e Especificidade , Virginia/epidemiologia
18.
J Zoo Wildl Med ; 50(4): 1012-1015, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926539

RESUMO

Adenoviruses have been reported to affect a broad range of host species, tend to be species specific, and often affect the respiratory system. This report describes the isolation of an adenovirus from deep nasal swabs of two wild North American porcupines (Erethizon dorsatum) with respiratory diseases that presented to a wildlife hospital. Partial sequences of the deoxyribonucleic acid polymerase gene of the isolated virus were identical to skunk adenovirus (SkAdV-1), also known as pygmy marmoset adenovirus. Both porcupines survived and were released back to the wild after successful medical treatment and rehabilitation. The significance of the adenovirus isolated from these porcupines is unknown; however, this is the first report of an adenovirus in porcupines, and the first report of SkAdV-1 in a rodent.


Assuntos
Infecções por Adenoviridae/veterinária , Adenoviridae/classificação , Porcos-Espinhos , Infecções Respiratórias/veterinária , Adenoviridae/isolamento & purificação , Infecções por Adenoviridae/tratamento farmacológico , Infecções por Adenoviridae/virologia , Animais , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Broncodilatadores/uso terapêutico , Enrofloxacina/uso terapêutico , Masculino , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/virologia , Terbutalina/uso terapêutico
19.
J Infect Dis ; 221(3): 379-388, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31541573

RESUMO

BACKGROUND: Hematopoietic cell transplant (HCT) recipients are frequently infected with respiratory viruses (RVs) in the upper respiratory tract (URT), but the concordance between URT and lower respiratory tract (LRT) RV detection is not well characterized. METHODS: Hematopoietic cell transplant candidates and recipients with respiratory symptoms and LRT and URT RV testing via multiplex PCR from 2009 to 2016 were included. Logistic regression models were used to analyze risk factors for LRT RV detection. RESULTS: Two-hundred thirty-five HCT candidates or recipients had URT and LRT RV testing within 3 days. Among 115 subjects (49%) positive for a RV, 37% (42 of 115) had discordant sample pairs. Forty percent (17 of 42) of discordant pairs were positive in the LRT but negative in the URT. Discordance was common for adenovirus (100%), metapneumovirus (44%), rhinovirus (34%), and parainfluenza virus type 3 (28%); respiratory syncytial virus was highly concordant (92%). Likelihood of LRT detection was increased with URT detection (oods ratio [OR] = 73.7; 95% confidence interval [CI], 26.7-204) and in cytomegalovirus-positive recipients (OR = 3.70; 95% CI, 1.30-10.0). CONCLUSIONS: High rates of discordance were observed for certain RVs. Bronchoalveolar lavage sampling may provide useful diagnostic information to guide management in symptomatic HCT candidates and recipients.


Assuntos
Infecções por Adenoviridae/diagnóstico , Adenoviridae/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Vírus Respiratório Sincicial/diagnóstico , Vírus Sinciciais Respiratórios/genética , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/etiologia , Infecções por Adenoviridae/virologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Prognóstico , Infecções por Vírus Respiratório Sincicial/virologia , Infecções Respiratórias/virologia , Estudos Retrospectivos , Fatores de Risco , Transplantados , Adulto Jovem
20.
FEBS J ; 287(1): 205-217, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31365788

RESUMO

The adenovirus (Ad) genome is believed to be packaged into the virion by forming a chromatin-like structure. The replicated viral genome is likely to be condensed through binding with viral core proteins before encapsidation. Replicated viral genomes accumulate in the central region of the nucleus, which we termed virus-induced postreplication (ViPR) body. However, the molecular mechanism by which the nuclear structure is reorganized and its functional significance in virus production are currently not understood. In this study, we found that viral packaging protein IVa2, but not capsid proteins, accumulated in the ViPR body. In addition, nucleolar chromatin regulatory proteins, nucleophosmin 1 (NPM1), upstream binding factor, and nucleolin accumulated in the ViPR body in late-stage Ad infection. NPM1 depletion increased the nuclease-resistant viral genome and delayed the ViPR body formation. These results suggested that structural changes in the infected cell nucleus depend on the formation of viral chromatin by host chromatin regulatory proteins. Because NPM1 depletion decreases production of the infectious virion, we propose that host factor-mediated viral chromatin remodeling and concomitant ViPR body formation are prerequisites for efficient encapsidation of Ad chromatin.


Assuntos
Infecções por Adenoviridae/virologia , Adenoviridae/genética , Replicação do DNA , DNA Viral/genética , Proteínas Nucleares/metabolismo , Proteínas Virais/metabolismo , Replicação Viral , Células A549 , Infecções por Adenoviridae/genética , Núcleo Celular/genética , Núcleo Celular/metabolismo , DNA Viral/metabolismo , Genoma Viral , Humanos , Proteínas Nucleares/genética , Proteínas Virais/genética , Montagem de Vírus
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